U.S. Pat. No. 4,895,841 discloses donepezil hydrochloride (I), chemically known as (±)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride, as cyclic amine compounds.

Donepezil hydrochloride (I) is a reversible inhibitor of the enzyme acetylcholinesterase useful in the treatment of mild to moderate dementia of the Alzheimer's type disease.
N-benzyl 4-formyl piperidine (II) is a key intermediate in the synthesis of donepezil.

The intermediate (II) can be obtained by using (methoxymethyl) triphenyl phosphonium chloride as a reagent as disclosed in EP0296560. However, this reaction is not only very expensive, but requires the reaction to take place under cryogenic conditions. Another method, such as disclosed in U.S. Pat. No. 4,895,841, employs pyridine-4-aldehyde in the synthesis of intermediate (II), which is followed by reduction of aromatic ring at last stage also involves very harsh reaction conditions.
There are many other processes known in the art to prepare donepezil hydrochloride, which are exemplified in patent applications such as WO2005076749, EP1531151 and WO2005003092.
The present invention is novel and relates to synthesis of donepezil hydrochloride using a novel synthetic intermediate. Thus, the object of the present invention is to provide a simple and industrially viable process for the synthesis of donepezil hydrochloride using a novel intermediate. This invention enables the synthesis of donepezil to be carried out in a cost effect manner and avoiding unfavorable reaction conditions.